Document Detail

ATM deficiency augments constitutively nuclear cyclin D1-driven genomic instability and lymphomagenesis.
MedLine Citation:
PMID:  23318439     Owner:  NLM     Status:  Publisher    
Cyclin D1 deregulation is implicated in the genesis of multiple human cancers. Importantly, nuclear cyclin D1 retention during S-phase promotes DNA re-replication and subsequent genomic instability, providing a direct correlation between aberrant cyclin D1/CDK4 activity, transcriptional regulation and double strand DNA break (DSB) induction. Together, these molecular events catalyze the genomic instability necessary for neoplastic transformation. Given that replication-associated DNA damage is central to cyclin D1-driven neoplasia, inactivation of critical checkpoint mediators should augment cyclin D1-dependent tumorigenesis in vivo. To interrogate potential synergy between constitutively nuclear cyclin D1 expression and impaired DSB-induced checkpoint integrity, Ataxia Telangiectasia Mutated (ATM)-deficient mice harboring the Eμ-D1T286A transgene were generated and evaluated for tumor onset. Eμ-D1T286A/ATM-/- mice exhibit dramatically accelerated incidence of both B- and T-cell lymphomas relative to Eμ-D1T286A or ATM-/- control cohorts. Lymphomas exhibit clonal chromosomal alterations distinct from ATM-/- mice, which typically acquire translocations involving the Tcrα/δ locus during V(D)J recombination, and instead harbor alterations at the c-Myc locus. Collectively, these findings reveal an intricate relationship wherein nuclear cyclin D1/CDK4 drives genomic instability in the absence of ATM function and clonal selection of cells harboring alterations within the murine c-Myc locus, ultimately facilitating transformation and tumor formation.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.577.
L P Vaites; Z Lian; E K Lee; B Yin; A Demicco; C H Bassing; J A Diehl
Related Documents :
23610439 - Microhomology-mediated end joining and homologous recombination share the initial end r...
24832099 - Papillomavirus genomes associate with brd4 to replicate at fragile sites in the host ge...
24480639 - An expanding world of small rnas.
24699249 - Dna repair pathway selection caused by defects in tel1, sae2, and de novo telomere addi...
22944079 - Detection and quantification of a radiation-associated mitochondrial dna deletion by a ...
23956629 - Screening of cell cycle-related genes of pleurotus eryngii using yeast mutant strains.
23352859 - Gas-phase synthesis of solid state dna nanoparticles stabilized by l-leucine.
2017369 - Actinomycin d induced dnase i hypersensitivity and asymmetric structure transmission in...
9092619 - Expression of functional elements inserted into the 35s promoter region of infectious c...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-14
Journal Detail:
Title:  Oncogene     Volume:  -     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1] The Leonard and Madlyn Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA [2] Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  WASF3 regulates miR-200 inactivation by ZEB1 through suppression of KISS1 leading to increased invas...
Next Document:  The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multip...